The first objective of this proposal is to study the antigenic determinants of human follicle stimulating hormone (hFSH). Although it is generally accepted that FSH mixed with adjuvant elicits an immune response, little is known about the immunodominant sites of hFSH and whether or not one subunit is more antigenic than the other. In addition nothing is known about the tertiary structure of hFSH and which parts of FSH are the receptor binding sites. Monoclonal antibodies to hFSH have been prepared but an epitope map of hFSH is needed which identifies paratopes for the sequential and conformational antigenic determinants (epitopes) of hFSH. Thus, synthetic peptides of alpha and beta subunit sequences will be synthesized and used to screen all hFSH Ab1 by an enzyme linked immunosorbent assay (ELISA). A second goal of this proposal is to study the formation of antiidiotypic antibodies to hFSH antibodies. If an antibody (Ab1) is produced against hFSH, then Ab1 can induce the production of a second antibody (Ab2) an antiidiotype which recognizes epitopes on Ab1. If Ab1 antigen binding site (paratope) binds to the receptor binding site of FSH, an antiidiotype (Ab2) which recognizes that paratope would be expected to bind to FSH receptor. These criteria are the hallmark of Ab which would be expected to bind to the receptor binding site of hFSH. Antiidiotypic inactivation of ovarian receptors or cytolytic complement fixation of antiidiotype-receptor complexes would be expected to result in ovarian failure. Monoclonal antibodies to hFSH which will be used as immunogen must not be able to bind to the HR complex and must block binding of FSH to receptor. Paratope specific antiidiotypic Ab2 will be determined by their ability to inhibit binding of FSH to anti-FSH. Antiidiotypic antibodies will also be tested for their ability to inhibit binding of FSH to receptors. The long term goals of the research are to elucidate the major antigenic sites of hFSH so that we may rationally design recombinant DNA encoding for the biologically active hormone but with sufficient amino acid substitutions in the antigenic sites to produce a poor immunogen with good clinical usefulness. Furthermore, understanding the antiidiotypic response to hFSH may allow the development of an antiidiotype contraceptive vaccine against hFSH without utilizing hFSH itself and with the potential for reversibility.